Our theme is the understanding and assessment of risk to human health from exposure to hazardous substances. We approach this theme from the perspective of an interdisciplinary team that integrates exposure assessment, biologic pathogenesis, and epidemiologic studies. Our biomedical studies revolve around three classes of illness: reproductive health, cardio-respiratory health, and cancer. Our non-biomedical studies relate to health of the ecosystem and to factors that affect aquatic organisms. These studies encompass specific exposures to metals and to organo-chlorine compounds. Reproductive health is being evaluated in relation to environmental exposure to lead, mercury, polychlorinated biphenyls (PCBs) and related compounds; cardio-respiratory health is being evaluated in relation to occupational exposure to fuel oil ash, which contains a high level of vanadium and other metals; the occurrence of cancer and its precursors are being evaluated in relation to arsenic in drinking water supplies; the health of the ecosystem, specifically of aquatic organisms, is being evaluated in relation to the presence of metals, PCBs, and polyaromatic hydrocarbons (PAHs). Our general goal is to evaluate the relation between chemicals in the environment and their relation to human ill health. Our objectives include the following: - to assess the use of calcium supplements to minimize the adverse effects of lead on the fetus - to assess uncertainties in development effects in children related to multiple environmental exposure to metals and organic compounds - to evaluate the effects of in utero exposure to ambient levels of PCBs on growth and development of the child and on female reproductive health. - to evaluate the cardiac and respiratory effects of fuel-ash oil on the human lung and to determine the mechanism through which vanadium and other metallic components of fuel-ash adversely effect the heart and the lung - to evaluate the nature of the association between arsenic and skin and skin bladder cancers and their precursors and to assess the epigenetic mechanisms through which arsenic may affect human health - to evaluate the effects of these and related chemicals on the aquatic ecosystem so that a comprehensive approach can be developed to assess the health of the ecosystem - to develop an approach for exposure assessment and health evaluation in the community that will enable enlightened interaction between scientists and the community.